A large percentage of the adult population suffers from insomnia in some form at some time in their lives. This may vary from a single episode of one night's duration to chronic conditions. Transient insomnia is an insomnia that is present for one to several days, and is less than one week in duration. Short term insomnia is an insomnia of one to three weeks in duration. Chronic insomnia is typically accepted to involve episodes greater than three (3) weeks in duration. The insomnia may further involve onset insomnia (difficulty in falling asleep) and/or maintenance insomnia (difficulty in maintaining uninterrupted sleep). It is well known that the sleep deprivation resulting from such insomnia adversely affects cognition, safety and quality of life.
Known treatments for insomnia include the administration of medication, either of the non-barbiturate or barbiturate type, shortly before bedtime. While both types of sedatives may be used to effectively treat insomnia, neither is without its undesirable side effects. Barbiturate type sedatives, such as secobarbital (sold by Eli Lilly and Company under the tradename of Seconal.RTM.) are general depressants. While effective, these medications are well known to lose their effectiveness after a few days. Furthermore, they are highly addictive and commonly abused. They are therefore no longer widely prescribed.
The groups of medications now most commonly used for the treatment of insomnia are the imidazopyridines, the pyrazolopyrimidines and the benzodiazepines. There is one available hypnotic in the imidazopyridine group, one in the pyrazolopyrimidine group and there are five in the benzodiazepine group. They differ significantly in half lives but are otherwise very similar and equally effective. They have supplanted the barbiturates as the principal treatment for insomnia because they have less addiction potential and are associated with less risk for suicide than the barbiturates unless taken with alcohol. However, these groups, too, are addictive and their wide usage draws concern as their potential side effects become more apparent. These side effects include daytime sedation, decreased cognitive abilities such as memory loss and feelings of agitation after the drug's therapeutic effects pass.
In my prior inventions which issued as U.S. Pat. Nos. 5,502,047 and 5,643,897, I disclosed the novel use of low dose doxepin, amitriptyline, trimipramine, trazodone and mixtures thereof in the treatment of chronic insomnia. These medications are normally prescribed in high dosages for use as antidepressants (150-300 mg). All these medications have long half-lives, take several days to reach a steady state and take a minimum of 3-4 weeks to effect change in depressive affect. As such, those of ordinary skill in the art would expect that it would take a minimum of several days and as long as a month for such medications to effect a correction of an insomnia and thus their usefulness in chronic insomnia. A thorough study of my data, however, reveals the surprising fact that many patients benefited from the medications from day one of administration. That means that these medications, that have literally no effect on depression in the first days of administration, can, even at very low doses, have an immediate effect on insomnia, even before reaching steady state. This suggests an immediate mechanism of action that is entirely different from its action after weeks of accumulation, seemingly a direct neurochemical effect on sleep-wake mechanisms, an effect that is not at all obvious and, in fact, entirely unexpected considering the pharmacokinetics of the medications and their usefulness, to date, only in chronic conditions. With that recognition I have gone on to treat subjects with transient and short term insomnia and have discovered that very low doses of the stated medications (doxepin, amitriptyline, trimipramine, trazadone and mixtures thereof) can have an immediate beneficial effect on the sleep of subjects with transient and short term insomnia and are, therefore, useful agents for the treatment of individuals suffering from transient and short term insomnia of any etiology including the circadian desynchronization of jet lag.